Targeting aids or landmarking devices have been employed in diagnostic imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. These devices, commonly referred to as fiducial markers, generally occur as two types: internally occurring markers that are inherent in the subject's anatomy; and externally positionable imaging aids that can be permanently or temporarily affixed to the body under analysis. External fiducial markers have also been proposed for use and have been used in other imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) as well as in imaging techniques such as MRI and CT. No effective internally positionable devices have been developed.
Imaging techniques such as PET and SPECT rely upon cellular uptake of suitable imaging solutions such as 2-deoxy-2-[18F]fluoro-D-glucose to provide accurate images of metabolically active tissue, including cancerous or abnormal tissue material. Malignant cells, such as those found in cancerous tumor tissue, generally exhibit elevated energy requirements resulting in elevated levels of glucose consumption or other functional processes. By comparison, surrounding tissue is less metabolically active. Imaging techniques such as PET make use of this differential in cellular glucose uptake or functional or molecular uptake by employing radiopharmaceutically tagged uptake solutions to demonstrate areas of interest for imaging and analysis. SPECT and PET with other radiotracers such as 18F-fluorodeoxyglucose, 18F-sodium fluoride, 11C-methionine, 11C-choline, 11C-acetate, 18F-fluorocholine, 18F-fluoroethylcholine, 11C-deoxyglucose, 15O-oxygen, 11C-carbon monoxide, 15O-water, 11C-butanol, 11C—N-methylspiperone, 18F—N-methylspiperone, 18F-spiperone, 11C-flumazenil, 11C-ACHC, 11C-tyrosine, 11C-thymidine, 18F-beta estradiol, 16 alpha 18F-fluoroestradiol, 18F-moabs can image, for example, regional glucose metabolism, bone tumors, amino acid uptake and protein synthesis, cell membrane proliferation, regional brain metabolism, metabolic rate of oxygen utilization, blood flow and proteins. While both PET and SPECT allow distinction of tumor from normal tissues, there are instances in which PET and SPECT are difficult to use as a single imaging modality.
One drawback of such radiopharmaceutically assisted imaging techniques is that the visualized area of increased tracer accumulation is best localized in comparison to known anatomical references in order to be precisely characterized and located in the subject's body. In order to be visualized in a PET or SPECT scan, the anatomical element of interest must also be capable of sufficient uptake of radioactivity to provide a detectable emission. Thus, localization can be accomplished using PET or SPECT when a known anatomical landmark also exhibits increased radiotracer uptake relative to the surrounding imaged tissues. In such instances, the landmark can provide a reference against which the region under study can be located, analyzed and measured. This requirement becomes problematic in regions of greater anatomical variation, and in regions which have little radiotracer uptake on scan. Such regions provide few reference landmarks which have levels of increased cellular glucose or other tracer uptake.
This problem becomes more pronounced in situations where imaging data generated from PET or SPECT scans are to be integrated with imaging data derived from other methods such as, e.g., MRI, CT, or ultrasound. As described in Wahl et al., “Anatometabolic Tumor Imaging: Fusions of FDG PET with CT or MRI to Localize Foci of Increased Activity,” J. Nucl. Med; 34 (7); 1190-1197, (1993) “metabolic” data generated from PET studies of specific anatomical regions have been fused with imaging data generated by MRI and/or CT to visualize “hot spots” generated by abnormal cellular activity. Such data have been registered to anatomical images generated by MRI and/or CT. In Thornton et al., “A Head Immobilization System for Radiation Simulation, CT, MRI, and PET Imaging,” Medical Dosimetry: 16; 51-56, (1991), contour tubing is permanently mounted to immobilizing masks used in simulation planning and during radiation treatment for both central nervous system and cranial and facial tumors. A suitable positron emission material such as a fluorine-18 solution is inserted in the tubes to provide a positron emission from the known external source. The authors describe an external marker system that provides a reference system for imaging correlation.
In the process described in the Wahl et al. reference, external fiducial markers were placed during both anatomic (CT and MRI) and metabolic (PET) studies. These external fiducial markers, as well as inherent internal anatomical landmarks, were used to reconstruct fused images from the various imaging studies. This permitted greater accuracy in localizing structures of interest.
U.S. Pat. No. 4,884,566 to Mountz et al. is directed to an externally positioned apparatus for defining a plane of an image through a portion of the body. The device includes a frame onto which a plurality of channels can be mounted. A suitable imaging material can be contained in the channels to provide reference markers during scanning.
The methods and devices described in the Wahl and Thornton references present difficulties when employed to visualize regions where greater patient-to-patient anatomical variation is encountered. Such regions often lack internal landmarks or accurate correlation with the positioning of external fiducial markers. The device disclosed in Mountz has an effective use in imaging more confined and rigid regions like the cranium. However, external devices such as the Mountz device or that disclosed in Thornton are not designed for marking internal imaging regions such as the chest, abdomen or pelvis. In addition, external markers do not localize deep anatomy.
In three-dimensional radiation treatment planning or intensity-modulated radiation therapy, the ability to visualize targets and critical structures is crucial. These critical structures are organs that receive radiation dose but are not themselves targets for treatment. Examples of critical structures include, but are not limited to, the optic chasm, esophagus, spinal cord, small and large bowels, rectum, kidneys, vaginal walls, etc. Knowledge of the location of critical structures, as well as the targeted tissue for treatment, permits more accurate targeting and precise administration of radiation dose and greater sparing or normal tissue radiation toxicity.
The problem can present in many situations, for example, when functional imaging is introduced into radiation treatment planning for thoracic cancers such as lung cancer. In such situations it is important to visualize critical structures, such as the esophagus, in a manner that will permit the radiation oncologist to locate and identify critical structures and to locate the target tissue to plan and administer therapeutic radiation dose in a precise and accurate manner. Critical structures, such as esophageal tissue, are difficult to visualize in PET due to relatively low metabolic uptake of radiopharmaceutically marker by the esophagus, particularly in relation to the target tumor. Under such circumstances, metabolic emission imaging techniques such as PET or SPECT are of limited utility.
References such as Wahl et al. have proposed fusing data produced from metabolic imaging techniques with data generated from other imaging techniques. However, accurate visualization of certain critical structures or targets can be difficult even in multiple imaging systems. MRI is particularly sensitive to moving tissue. Even a stationary-positioned patient will produce motion from breathing, heart rate or peristalsis which can create image displacement or edge blurring artifacts. MRI motion artifact correction techniques such as retrospective triggering and respiratory compensation as well as gradient motion compensation do not completely remove motion artifacts from an MRI image, (Brown et al. “MRI Imaging, Abbreviations, Definitions and Descriptions: A Review,” Radiology (1999) 213 (3): 647.) Deep anatomy fiducial markers can facilitate inclusion of MRI imaging in multi-imaging modality fusion by complementing existing MRI artifact correction techniques.
The sensitivity and specificity of ultrasound is limited when applied to the study of small and deep anatomic structures. The utility of ultrasound imaging for multimodality image fusion would be enhanced through the use of an internal fiducial marker containing contrast agents that produce a homogeneous transmission of sound, harmonics or echogenicity. When targets and critical structures can be visualized by imaging techniques such as but not limited to PET, SPECT, MRI, ultrasound, CT or mammography, the ability to obtain fused multi-imaging data is limited, due, in part, to the absence of effective constant landmarks such as internal fiducial markers.
Based on the limitations of the imaging modalities described above, it is desirable to have means for more accurately identifying internal critical structures in various imaging techniques. It is also desirable to provide utility for maximum use of existing techniques for demonstrating morphologic and molecular disease. This is one of the research priorities of the U.S. National Institutes of Health.